Use of Radioisotopes in Assessment of Distal Blood Flow and Distal Blood Pressure in Arterial Insufficiency

Symposium on Vascular Surgery

Use of Radioisotopes in Assessment of Distal Blood Flow and Distal Blood Pressure in Arterial Insufficiency

N. A. Lassen, MD., Ph.D.,* and P. Holstein, MD.**

By recording the local clearance of radioactive isotopes in patients with arterial occlusive disease one can measure blood flow as well as blood pressure in muscles and skin distal of the occlusion. Distal blood flow is most conveniently measured as the muscle blood flow in the calf during hyperemia. This affords a sensitive diagnostic tool disclosing the presence of occlusive arterial lesions and it gives, in addition, some information regarding the site of this lesion. The distal blood pressure can also be measured in the muscles. But, we most often make these measurements in the skin on foot or leg because of the clinical usefulness of these measurements in treating impending or manifest ischemic skin lesions. This article will thus be confined to a discussion of distal blood flow in the calf muscles and of distal blood pressure in the skin. The clinical value will be compared to that of other methods for measurement of flow and pressure below the arterial occlusion. As such physiologic measurements afford a key to the proper therapy, we shall also comment both on surgical and on medical therapy.

Local Clearance Method Both radioisotopic techniques that will be described in this article are based on the local clearance method. The method was developed by Kety/3 who in 1949 used the disappearance rate of radioactive sodium (24Na+) injected intramuscularly as a measure of muscle blood flow. Walder in 1958 demonstrated with this method that there is a reduced

"'Chief, Department of Clinical Physiology, Bispebjerg Hospital, Copenhagen, Denmark """Department of Clinical Physiology, Bispebjerg Hospital, Copenhagen, Denmark

Surgical Clinics of North America- VoL 54, No.1, February 1974

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calf muscle blood flow during leg exercise in patients with arterial insufficiency of the leg. 25 He also showed that there is a much prolonged postexercise hyperemic response. There have been d~scribed other radioisotopic methods for the evaluation of arterial insufficiency. The delayed arrival in the foot of intravenously injected radioactive tracers 6 and the distribution in the leg tissues of macroaggregated radio-iodinated serum albumin l2 , 21 should in particular be mentioned. But these methods do not yield quantitative measures of blood flow or blood pressure in the distal tissues and have not found wider clinical application. The local clearance method is based on the use of tracers that diffuse so freely between the tissue and the capillary blood that diffusion equilibrium is practically maintained regardless of the rate of blood flow. For these tracers it is the blood flow that is the limiting factor in the removal from a locally injected depot. Among suchfiow limited tracers are the radioactive inert gas 133Xenon and 4-iodo-antipyrine labelled with 123Iodine or with 131 Iodine. Small ionized tracer molecules such as 24Sodium or 99mTechnetium (as pertechnetate) pass, on the other hand, more slowly across the capillary membrane. This means that during maximal hyperemia, at least in skeletal muscle, it is predominantly the capillary diffusion capacity (the permeability) which determines the rate of removal by the blood. Such tracers are thus mainly diffusion limited during hyperemia. But, at the very low flow that prevails when we measure distal blood pressure (see below) the small ions can be assumed to reach close to diffusion equilibrium between tissue and blood. Hence, in such measurements even these tracers are predominantly flow limited.

PRINCIPLE OF MUSCLE BLOOD FLOW For measurement of muscle blood flow we use radioactive Xenon, about 0.1 ml. of sterile saline containing 133Xe in physical solution (ca. 0.5 f..tc. per ml.) is injected intramuscularly. The injection causes a moderate hyperemic reaction as evidenced by a slightly faster washout rate during the initial few minutes. This injection artifact is normally quite small and the measured blood flow relates quite closely to true muscle blood flow when measurement is made a few minutes after the injection. 23 No adverse local reactions have been encountered, not even in patients with poor peripheral circulation. The only technical error of importance is the occasional deposition of the injectate in nonmuscle tissue, probably in adipose tissue. This error is encountered in about 1 per cent of injections and is recognized by a slowly decreasing clearance curve, which is unaffected by muscle exercise and which cannot be reproduced. Histamine is in some studies admixed to the l:l:lXe-saline (20 f..tg. per 0.1 ml.) in order to produce local hyperemia. The principle of measurement involves the recording of the disappearance of the 133Xe from the local depot by using a scintillation detector coupled to a ratemeter. The calculation of the muscle blood flow (MBF) is made from the slope of the logarithmically recorded washout curve. This slope is proportional to the flow, a shallow slope corresponding to a slow \

41

USE OF RADIOISOTOPES IN ASSESSMENT OF ARTERIAL INSUFFICIENCY 1.0 0.8

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minutes after ischaemia and exercise

Figure 1. 133Xe clearance curves from the anterior tibialis muscle in a normal subject and in a patient with obliterative arterial disease. Muscle hyperaemia is provoked by ischaemia and exercise. A delayed hyperaemia response is pathognomonic of the disease.

flow, a steep slope to a fast flow. The factor of proportionality is 161 if the flow, D, is measured as a fraction of 100 per minute: MBF

=

161 x D ml. per 100 gm. per min.!

Measured by this method resting muscle blood flow is normally about 2 ml. per 100 gm. per min. in good agreement with estimates by plethysmographic techniques. During exercise the maximal muscle blood flow reaches levels of about 60 ml. per 100 gm. per min. in healthy adults.

Muscle Blood Flow in Occlusive Arterial Disease We originally employed ischemia combined with exercise as a stimulus for eliciting muscle hyperemiaY In this ischemic exercise test the subject is studied in the supine position and the 133Xe-saline is injected into the anterior tibial muscle, both sides being studied simultaneously (Fig. 1). After isotope injection the circulation to the legs is suddenly arrested by inflating cuffs placed above the knees. During the following 5 minutes the ischemia is maintained and the calf muscles are exercised to the point of fatigue and pain by ankle movements. When the cuff is suddenly released the clearance will in normal man increase to high levels corresponding to a muscle blood flow exceeding 35 ml. per 100 gm. per min. And this maximum is reached within about 20 seconds, maximally within 1 minute after cuff release. In patients with occlusive arterial disease the maximal flow is lower and it is reached more slowly. Some patients cannot cooperate in this test, failing to exercise the muscles to exhaustion. In such cases, one may use 5 minutes of ischemia alone, but then it is necessary to inject histamine along with the t:l3Xe, as otherwise the accuracy of the test suffers.!7 These tests are positive in about 95 per cent of patients with arterial occlusion between the heart and the site of measurement. Failures are encountered in cases with good collaterals and occlusion quite close to the site of measurement. Because of these failures and because of the discomfort to the patient as well as the undesirability of employing occluding cuffs if it can be avoided, we now use only the ischemic exercise test in patients who cannot perform the walking test.

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The walking test is made by injecting the 133Xe-saline into the calf muscles (Fig. 2).1. 2 Usually the medial head of the gastrocnemius muscle is studied. Light scintillation detectors are taped over the isotope depots, and after recording the resting clearance in the motionless standing position for about 2 minutes, the subject starts walking on a treadmill at a speed and elevation causing his typical symptoms to develop within about 2 minutes. Subjects not manifesting claudication are stopped after 3 to 5 minutes. After the walking test the patient stands motionless on the treadmill until the postexercise hyperemic phase has passed and a slow, fairly constant clearance rate approximating the pre-exercise resting value has become established. With this test the normal response consists of a muscle blood flow exceeding 10 ml per 100 gm. per min., and of a postexercise hyperemic period lasting less than 3 minutes. The patients usually have a lower blood flow during walking and they all have a delayed hyperemic response. The delay of maximal blood flow is a rough measure of the localization of the occlusion. Thus longer occlusions involving both the femoral and iliac arteries give a marked delay with the maximal postexercise hyperemia first being encountered with a delay of 4 minutes or more. The walking test involves little discomfort and no risk to the patient. The entire test including calculations and evaluation requires 30 minutes and is performed by a nurse or a technician. It has proved reliable provided one really does inject that muscle giving pain. In cases of branch thrombosis below the knee, it gives diagnostic possibilities that cannot readily be obtained by calf plethysmography (Fig. 3). Comments on the Routine Use of Muscle Blood Flow Measurements The blood flow value obtained with the l:J3Xe method is not very reproducible as it has a coefficient of variation of about 25 per cent. But the diagnostic criteria also include an evaluation of the shape of the 133Xe washout curve. And using both flow and time course there is quite a wide and clearcut difference between normal and abnormal responses (Fig. 4). The variability in blood flow values does not invalidate the clinical routine use of the method. 1.0r-------Tr~~~~--------------------------------------_,

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Figure 2. 133Xe clearance curves from the gastrocnemius muscle in a normal subject and in a patient with obliterative arterial disease. The muscle hyperaemia is provoked by strenuous walking on a treadmill causing intermittent claudication in most patients with this complaint. The typical delayed hyperaemia in the patient corresponds to the pattern of the postischaemic-exercise test (Fig. 1).

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USE OF RADIOISOTOPES IN ASSESSMENT OF ARTERIAL INSUFFICIENCY

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anterior tibial muscle (right)

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Figure 3. 133Xe walking test performed in a patient with bilateral branch thrombosis of the posterior tibial artery. In the first test (left upper and lower panels) the isotope was injected into the anterior tibial muscle in both legs and the walking test was normal as can be seen from the figure. In the second test (right upper and lower panels) the isotope was injected into the medial head of the gastrocnemius muscle and here the maximal blood flow was delayed and the resting-clearance was not established until 8 to 10 minutes later. The angiogram showed occlusion of the posterior tibial artery in both legs, whereas the anterior tibial artery was intact as was the proximal arterial tree.

The 133Xe method can of course also be used for physiologic studies of muscle blood flow. Then a fairly large number of observations are often needed in order to reduce the random variation. We cannot here give an account of the various scientific results thus obtained. It may be appropriate, however, to tell that the spectacular improvement in walking tolerance that can be regularly obtained by exercise training of claudicants is associated with only a small increase in calf muscle blood flow during walking. Enzymatic adaptation10 and not development of new collaterals is apparently the main mechanism of this therapy, which is so far the only form of conservative treatment of established value in patients with intermittent claudication. Compared to calf plethysmography as applied to blood flow measurement, the 133){e method has the advantage of ease of performance: external compressing cuffs can usually be avoided and no standardization is needed (same normal and abnormal values have been found in various laboratories). In our experience the two blood flow methods are about equally effective (the advantage of 133Xe in diagnosis of branch thrombosis has already been mentioned). In practically all cases they permit one to establish the diagnosis so that angiography can be reserved for use in situations when a surgical intervention must be considered. With the

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Figure 4. Timecourse of the '33Xe washout curve from calf muscles: the relation between the duration of post-exercise hyperaemia and the percentage of hyperaemia after 1 minute of rest. Normal values (mean + 2 S.D.) are shown by the shaded area. The values from 52 calf muscles in 18 legs with arterial occlusion above the knee differ widely from the normals.'

benign spontaneous prognosis and with the symptomatic improvement obtained by walking exercise, reconstructive surgery is in our experience rarely indicated in elderly claudicants if they do not suffer in addition from severe distal hypotension at rest, as will be discussed below.

PRINCIPLE OF SKIN BLOOD PRESSURE Assessment of the arterial blood pressure in a tissue as that external counterpressure which just suffices to arrest tissue blood flow was introduced in 1967. 7 • 20 The flow cessation pressure measured by inflating a blood pressure cuff placed over a radioactive depot injected intramuscularly was found to be practically equal to the diastolic blood pressure in normal subjects. In patients with severe occlusive arterial disease this pressure is markedly reduced. This principle has been adapted here for measuring the local blood pressure in the skin. We use 4-iodo-antipyrine labeled with 131Iodine or 125Iodine dissolved in sterile water at a concentration of about 0.2 f-Lc. per ml. Histamine is always admixed to the radioactive solution, so that the injectate contains 50 f-Lg. per 0.1 ml. This results in vasodilatation of the skin and minimizes the influence of temperature induced spontaneous variations in skin blood flow. 131Iodide (Na131 I) can also be used. 133Xe is not practical due to diffusion of this tracer into the subcutaneous adipose tissue in which it

USE OF RADIOISOTOPES IN ASSESSMENT OF ARTERIAL INSUFFICIENCY

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has a high solubility and 99mpertechnetate is washed out too slowly to allow exact interpretation of the clearance curve. About 0.1 ml. of the tracer-histamine mixture is injected intradermally, so that a small papule is raised. The counterpressure is obtained by placing a conventional arm blood pressure cuff, so that it covers the depot. In order to measure the local pressure over the injected skin area even more precisely, we employ in addition a small, thin-walled plastic bag that is interposed between the depot and the blood pressure cuff. The bag is filled with a small amount of air (or water) and connected to a manometer (Fig. 5). It is this manometer and not that which one could connect to the outer cuff that we employ. The small plastic bag overlies the injected skin area smoothly (without wrinkles) even where the surface is irregular, as on the foot. A scintillation detector is placed over the blood pressure cuff at a distance of about 10 cm. from the depot and the clearance is recorded semilogarithmically. When a constant clearance (a descending straight line) has been observed for about 3 minutes with no counterpressure applied, then this pressure is raised stepwise resulting in a stepwise decrease in isotope washout rate (Fig. 6). In order to determine the pressure at which the clearance stops it is necessary at the highest pressure steps (made at intervals of 5 mm. Hg) to observe the curve for about 5 minutes at each Recorder Ratemeter

Figure 5. Measurement of skin blood pressure on the calf by the flow cessation counter pressure. The local clearance from an intradermal depot of 131I-antipyrine mixed with histamine is registered by a scintillation detector coupled to a ratemeter, the output of which is recorded on a pen writer. Counterpressure to the depot is applied with an ordinary blood pressure cuff. A plastic bag containing a small amount of air is interposed between the cuff and the depot, and the pressure directly to the depot is measured by a manometer connected to this bag.

N. A.

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Log CPS SKIN BLOOD PRESSURE: 48 mmHg

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Figure 6. The local clearance from an intradermal depot of I3II-antipyrine mixed with histamine. Stepwise increasing counter pressure results in a stepwise decrease in clearance until flow cessation occurs (flat curve).

\ /

o SKIN BLOOD PRESSURE IN NORMAL SUBJECT ARM BLOOD PRESSURE

SKIN BLOOD PRESSURE IN OCCLUSION OF FEMORAL ARTERIES 14%5 ARM BLOOD PRESSURE

Figure 7. Skin blood pressure measured on both legs in a normal subject at various levels (left), and in a patient with vascular occlusive disease (right). In the patient's right leg there is an occlusion of the superficial femoral artery. In the left leg there is an occlusion of both the superficial and the deep femoral artery. Gangrene of the toes on the left leg was present. The skin pressure values are adjusted to one arm blood pressure level in each patient.

USE OF RADIOISOTOPES iN ASSESSMENT OF ARTERIAL INSUFFICIENCY

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step. The skin blood pressure is taken to be the pressure midway between the highest pressure at which flow still can be discerned and the pressure level above this at which flow cessation is observed. The most important source of error is the movement artifact. The leg must be kept immobile at a constant distance from the detector and this demands proper fixation of the leg. We use sandbags. Another source of error which is related to the movement artifact is seen when the skin is edematous. Then the external compression moving the fluid will cause the skin to move away from the detector. In case of edema the swelling should be squeezed away by applying a pressure of about 80 mm. Hg for 2 to 3 minutes prior to the study. The room temperature should be "thermoneutral" (ca. 25° C.), so that the patient feels comfortable with light clothing and the skin temperature is warm (ca. 28 to 32° C). Arm blood pressure should always be taken simultaneously. We block the thyroid by 0.5 gm. of potassium iodide before injecting iodine containing tracers. Skin Blood Pressure in Occlusive Arterial Disease In normal man the external pressure on the skin which results in flow cessation lies close to the diastolic blood pressure regardless of the site measured from (Fig. 7). By external compression of a tissue the situation created is equivalent to a decrease of the arterial blood pressure. The observation in normal man implies, therefore, that when the effective local diastolic blood pressure is zero, then flow also stops. Why this is so we do not know. The relation between flow cessation in the skin and diastolic blood pressure can probably be disrupted. Extreme bradycardia or marked tachycardia might do so. Severe hypertension or other conditions with marked pulse pressure might also cause the flow cessation pressure to be higher than the diastolic one. But in personal studies of patients with essential hypertension we have so far not encountered such cases. It follows from the above considerations that in patients with occlusive arterial disease where the pulse pressure in the distal vascular bed is decreased, the skin blood pressure is a measure of the local diastolic blood pressure. This pressure is often normal in patients with claudication, while in patients with chronic ischemic skin lesions or rest pain the local pressure is invariably below 20 to 30 mm. Hg. In such low pressure areas skin lesions heal badly or not at all. This observation we consider of decisive clinical importance, as is illustrated by a series of major leg amputations recently studied in our clinic: 2 to 8 weeks after surgery skin blood pressure was measured on the anterolateral side of the stump 10 cm. from the wound (Fig. 8). Of the 51 cases reamputation at a more proximal level because of ischemic skin necrosis became necessary in 8 cases. The skin blood pressure at the level of the amputation was low in all 8 cases. If we divide the material into legs with skin pressures below 20 mm. Hg, between 20 and 40 mm. Hg, and above 40 mm. Hg, the result obtained was that (1) 5 out of 5 amputations with a skin blood pressure below 20 mm. Hg failed because of ischemic necrosis; (2) 3 out of 12 amputations with a skin blood pressure between 20 and 40 mm. Hg failed

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22 ABOVE-KNEE STUMPS 29 BELOW-KNEE STUMPS

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Failure because of ischaemic skin necrosis Failure because of

L!.J gross wound infection

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Failure because of large haematoma

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Primary healing

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100 mm Hg

Figure 8. Skin blood pressure values measured 2 to 8 weeks postoperatively in 51 amputation stumps (29 below knee and 22 above knee). Ischaemic skin necrosis invariably caused reamputation when the skin blood pressure was below 20 mm. Hg. Between 20 and 39 mm. Hg skin necrosis resulted in failure or slow secondary wound healing in most cases. Among 34 stumps with a skin blood pressure of 40 mm. Hg or more there were three failures, due to wound infection or haematoma, but no failures because of skin necrosis.

because of ischemic necrosis; (3) none of 34 amputations with a skin blood pressure above 40 mm. Hg failed because of ischemic necrosis. Secondary wound healing occurred in 11 subjects. It was our clinical impression that this complication was in many cases related to poor skin circulation especially where the skin sutures had been placed. This impression gains support by the skin blood pressure measurements showing many such cases in the 20 to 40 mm. Hg group. It shall not be claimed that an adequate skin perfusion pressure is a guarantee against wound failure. There were 3 failures at high pressures, 2 severe infections and 1 large haematoma compromising the surgery. But, if the pressure is very low, then it appears that a large wound (the amputation) cannot heal. This is amply supported by our experience concerning the healing of traumatic or "spontaneous" skin lesions in patients with occlusive arterial disease: if the skin blood pressure is below approximately 20 mm. Hg, healing will not occur; in the pressure range 20 to 40 mm. Hg slow healing will usually occur; if the pressure is higher, then circulation is not a problem. In the amputation material presented we gave the postoperative pressure because it corresponds to the pressure when healing must occur. The clinically important problem is, however, the preoperative assessment of the skin blood pressure. In most cases this pressure corresponds closely to the postoperative one, so that correct prognostic inferences could be drawn (Fig. 9). In low pressure regions the trauma of operation and bandage pressure may cause skin necrosis of extensive areas in which the pressure decreases to zero. But in other cases a moderate pressure rise was found postoperatively, and hence the chances of healing

USE OF RADIOISOTOPES IN ASSESSMENT OF ARTERIAL INSUFFICIENCY

SKIN BLOOD PRESSURE AT THE AMPUTATION LEVEL (BELOW KNEE)

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SKIN BLOOD PRESSURE ON THE CONTRALATERAL LEG (CALF)

mmHg.-________________~ PREOP

POSTOP

PREOP

POS

100

80

60

1 ___------~L-~~

=_

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28 PATIENTS

Figure 9. Skin blood pressure in 28 below-knee amputations. Left column: Skin blood pressure measured preoperatively approximately 10 em. proximal to the amputation level and again at the same site 2 to 8 weeks after surgery. The postoperative values are corrected parallel to changes in diastolic arm blood pressure (except from two zero-values). An increase in pressure after amputation is apparent in 11 cases (p < 0.01). Right column: Pre- and postoperative skin blood pressure measured as a control on the contralateral leg usually on the calf. Postoperative values corrected parallel to changes in arm diastolic pressure. The values are fairly constant, S.D. 5 mm. Hg.

would be considered better on the basis of the postoperative values than on the basis of the preoperative value. This pressure rise is related to the surgical removal of a sizeable part of the distal runoff tissues. It occurs regularly if the amputation is made rather close to the site of the critical vascular occlusion. One can preoperatively mimic this effect by applying a tourniquet at the-level considered for amputation. With this maneuver ("pseudoamputation") the skin blood pressure proximal to the tourniquet will immediately rise approximately to its postoperative level. Unfortunately one cannot carry through this pseudoamputation while measuring with the radioisotopic technique. This is so because a long time (20 minutes or so) is necessary to measure the pressure, and the patients cannot tolerate this prolonged ischemia because of severe pains. For assessing skin pressure during pseudoamputation we routinely use a photoelectric technique (Fig. 10).19

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t - - POSTOP.---i

PREOP. Skin blood pressure (photoelectric) (isotope)

Figure 10. Skin blood pressure on the calf in a patient with gangrene of the foot measured with the isotope technique and a photoelectric technique. During pseudoamputation with a tourniquet, the skin blood pressure increased to about 50 mm. Hg. The procedure was repeated to secure reproducibility. Three weeks after successful below-knee amputation the skin blood pressure was again measured at the same site and the values corresponded to those obtained during the preoperative pseudoamputation (case 1).

CASE HISTORY

I

A 68 year old male suffered from severe resting pain and gangrene of the left foot. Normal pulses could be felt in the femoral arteries. The skin blood pressure measured with the isotope technique 10 cm. distal to the patella was 23 mm. Hg and about 25 mm. Hg as measured with a photoelectric technique. During pseudoamputation with a tourniquet at the level considered suitable for amputation, the skin blood pressure measured just proximal to the tourniquet increased to about 50 mm. Hg (see Fig. 10). A below-knee amputation was performed and healed primarily. Three weeks after surgery the skin blood pressure was again measured and values corresponding to those obtained during the preoperative pseudoamputation were found.

It should be noted that the standard technique of measurement with radioisotopes entails an element of pseudoamputation, because the cuff encircling the limb reduces the flow, but only a suprasystolic counter pressure will stop the circulation distal to the cuff completely and give a complete pseudoamputation effect.

Comments on the Routine Use of Skin Blood Pressure Measurements The skin blood pressure is a measure of the distal arterial blood pressure. This distal pressure is, other factors being equal, such as the thermoneutrality and complete rest, a function of the proximal (aortic) pressure. We observe that the skin blood pressure in our patients varies in parallel with the variations in diastolic arm blood pressure. When this pressure is reasonably constant, then skin blood pressure is reproducible with a standard deviation of only 5 mm. Hg. This high accuracy is undoubtedly related to the integration caused by the prolonged observation periods of about 5 minutes at each of the "final" pressure steps made. If consistent variations in arm diastolic blood pressure are observed by repeated measurements, then a correction for such variations must be made.

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The measurement of skin blood pressure has for some years been used routinely in our clinic for evaluating the prognosis and selecting the proper therapy. Spontaneous healing of small ischemic skin lesions is not uncommon. These patients are easily recognized by having a distal blood pressure of approximately 30 mm. Hg or more. They require no urgent therapy, but are usually candidates for elective reconstructive surgery. We also see patients who suffer from intermittent claudication, and although they have no resting pain and no ulcerations, the distal blood pressure may be below 30 mm. Hg. This means that a skin lesion will not heal and often initiates a gangrene. These patients are therefore also potential candidates for reconstructive surgery. And, if other diseases or old age does not contraindicate surgery, an angiographic study should consequently be considered. Surgery is of course the only radical way of repressurization of the distal arterial tree. But if reconstructive surgery cannot be performed or has failed, then a conservative medical treatment will in many cases result in healing of smaller chronic ischemic lesions in skin areas where the pressure is borderline with regard to wound healing, i.e., 25 to 35 mm. Hg. Simple classical measures such as elevating the head end of the bed and leg exercise as recommended by Buerger are helpful in improving the local circulation. Local skin compression must be avoided, and all types of drugs that tend to lower the systemic blood pressure and hence the distal pressure should be withdrawn if at all possible. In many old patients, stopping the use of diuretics may allow a small ischemic skin lesion to heal or rest pain to disappear. Ed~ma should be prevented by avoiding dependent position of the legs for longer periods -not with diuretics. We consider sympathectomy to be contraindicated because it tends to lower an already critically low distal pressure. '8 A more active form of medical treatment involves the elevation of the systemic blood pressure using the synthetic mineralocorticoid (l!fluor-hydrocortisone (Florinef). By inducing moderate hypertension also the leg blood pressure rises and the ischemic skin lesions heal over some months if the local pressure can be maintained above 30 to 40 mm. Hg. In a recent series 51 out of 72 such treatments resulted in healing of chronic gangrenous ulcers which otherwise would have resulted in amputation. '4. '6 In cases with the lowest skin blood pressure or where heart disease in preexisting arterial hypertension contraindicates the "medical repressurization," or in cases with already extensive necrotic lesions, amputation cannot be avoided. Here we employ the pressure measurements as a guide in selection of the proper level. ' !

CASE HISTORY

2

56 year old diabetic female with gangrene of the fifth toe on the right foot. Skin blood pressure on the dorsal side of the foot was 58 mm. Hg (arm blood pressure 140/70). A local resection of the necrotic tissues was carried out and the wound healed primarily (Fig. 11).

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Figure 11.

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Pre- and postoperative appearance (case 2).

CASE HISTORY

3

51 year old male, above-knee amputee on the left side, now suffered from severe resting pain and gangrene of the right foot. Attempt of vascular reconstructive surgery was without success. The skin blood pressure on the calf was 13 mm. Hg and no increase could be registered during pseudoamputation. Despite this low pressure a below-knee amputation was performed in the hope of salvaging his remaining knee. Surgery was performed with meticulous care. Postoperative skin blood pressure was unchanged at the low preoperative level. No sign of wound healing could be noted. There were no clinical signs of infection and repeated swabs did not reveal bacterial growth. Increasing skin necrosis and pain necessitated an above-knee reamputation 4 weeks later (Fig. 12).

To amputate as soon as the hopeless prognosis can be ascertained and at the correct level is mandatory for survival and the quality of the survival (general health and walking ability) of these often fragile patients.

Figure 12. Below-knee amputation stump 1,2, and 4 weeks after surgery. Low pressure area with increasing skin necrosis and no wound healing (case 3).

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This outline of the clinical use of skin blood pressure cannot do justice to many special problems. Diabetic skin lesions constitute such a problem. We just want to point out that skin lesions in diabetics heal just as in nondiabetics, i.e., if the skin blood pressure is above ca. 30 to 40 mm. Hg, provided infection is combatted and external pressure is not allowed to compromise skin circulation.

WHY USE RADIOACTIVE ISOTOPES? The clinical diagnosis of occlusive arterial disease can be confirmed by a number of sensitive objective tests. In our opinion at least one such test should be used to confirm the clinical impression. The objective examination, in particular pulse palpation, is not sufficiently precise. The presence of palpable distal pulses does not rule out significant obstructive arterial lesions in the main artery. And as already mentioned, arteriography should not be necessary in most mild cases as surgical intervention is not indicated. But how to choose the simplest and yet most reliable test? Shall we use oscillometry? Digital pulse morphology? Blood flow measurement with 133Xe or plethysmography? Without giving a detailed discussion of such tests and their relative merits, we shall express the opinion that measurements of the ankle blood pressure by the use of the Doppler shift ultrasound detector4 • 24. 26 or, as in our practice, the mercury in Silas tic strain gauge,3. 8. 9. 22 which allows a measure of toe blood pressure too, are the best methods now available. These tests readily allow one to measure the whole span of pressures from over 200 mm. Hg to below 10 mm. Hg. Their diagnostic reliability is very high and, what is of great practical value, the results are expressed in millimeters of mercury, the clinical importance of which is immediately understandable for doctors and nurses, yes even for the patients. However, we continue, in addition to distal systolic blood pressure measurements, to use the 133Xe walking test in a great many cases. Objective assessment of the walking distance on a treadmill with adjustable speed and elevation is in our experience indispensable in claudicants. Then a 133Xe flow study is easily added" and, in certain cases of branch thrombosis, only this test gives the correct diagnosis. With regard to assessment of the prognosis in severe cases of leg ischemia, the distal systolic blood pressure measured by the strain gauge technique is also very useful. But in many such patients the pressure on the first toe cannot be measured because of ulcerations. The most important limitation, however, is in our experience the variability of the results in the lowest pressure range. If the cuff is applied too loosely the pressure is overestimated; if it is too tight the pressure is underestimated. Cases of increased wall stiffness also occur. Apparently in external compression of the microcirculation of the skin as in the radioisotope method, the pressure transmission from cuff interior (the small PVC cushion) to the venules of the skin is more reliable. Moreover, one cannot measure the blood pressure in a given skin area with the strain gauge; this value pertains to that large artery in the cross section encircled by the cuff which

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HOLSTEIN

has the highest blood pressure. It has not been our experience that we can predict the prognosis of ischemic skin lesions (and select amputation levels) with the same reliability with strain gauge as with the isotope method. We are eager to abandon the skin blood pressure technique. To inject the isotope intradermally is in principle unattractive in gangrene and pre gangrene cases. And the test is time consuIning and causes discomfort. But then we must have another test that is safer and simpler, e.g., based on photoelectric recording of skin reddening as commented on above or another principle. To be without these pressures after having learned their value in patient management, we could not readily accept. In this article we have emphasized the value of pressure over that of flow. Yet it cannot be disagreed that blood flow is what the tissues demand. Would it not after all be best to measure skin flow? No, probably not. Skin flow is very variable. What the blood pressure tells is the potentiality for flow: when blood pressure is high, blood flow may also have the possibility of becoming high, i.e., of responding to increased tissue demand.

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USE OF RADIOISOTOPES IN ASSESSMENT OF ARTERIAL INSUFFICIENCY

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